More than a hundred human genomic regions relevant to cancer have been identified by combining genetic, cytogenetic and molecular analysis of both inherited and non-inherited tumors. Our investigations have been focusing on two genomic regions of chromosomes 11 and 21 relevant to genomic rearrangements of childhood tumors and associated to inherited and constitutional disorders. Both regions also contain genes of the ETS family actively studied in this Laboratory. The 11q23 region contains the loci for conditions predisposing to both benign and malignant tumors, such as tuberous sclerosis and ataxia telangiectasia. A number of acquired genomic abnormalities specific to acute leukemia and small round-cell tumors of childhood, such as Ewing's sarcoma and neuroepithelioma implicate the same region. ETS1 has been located in the 11q23 band. The 21q22 region is of genetic relevance since it is pathogenetic, when trisomic, for Down's syndrome. This constitutional aneuploidy is associated to leukemia and to a curious transient myeloproliferative disorder of newborns. Two genes of the ETS family, ETS2 and ERG, are located in the region.